Intracellular calcium homeostasis and its dysregulation underlying epileptic seizures.

Biological activities require a delicate balance between excitatory and inhibitory signals in the brain. Disruption of this balance could lead to neurological disorders, such as epilepsydue to a relative enhancement of excitatory signals. In general, cytosolic calcium plays a key role in the transmission of excitatory signals mainly by promoting the release of synaptic vesicles containing neurotransmitters. A series of molecular components responsible for maintaining intracellular calcium homeostasis, including voltage-gated calcium (CaV) channels, the endoplasmic reticulum (ER) calcium sensor stromal interaction molecule (STIM), the PM calcium channel Orai, ER-resident inositol trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), sarco-endoplasmic reticulum calcium ATPase (SERCA), and transmembrane and coiled-coil domains 1 (TMCO1), have been demonstrated to be involved in calcium dysregulation that underlies epileptic seizures. More importantly, epileptic phenotypes were confirmed in several molecular components by transgenic animal models, including CACNA1A, CACNA1E, CACNA1G, CACNA2D1, ORAI1 and IP3R1. Calcium-binding proteins (CaBPs), such as calmodulin, parvalbumin, calretinin, and calbindin, provide an additional layer of defense by acting as calcium reservoirs to buffer rapid increases in cytosolic calcium concentrations and participate in cellular functions by regulating the activities of ion channels or acting as calcium-modulated sensors, and a series of lines of evidence support their implication with epileptic activities. Overall, stroke represents the most common environmental cause of acquired epilepsy in older adults, and preventing calcium disruption due to reperfusion injury might be an effective way to treat acute symptomatic seizures and decrease the risk for acquired poststroke epilepsy.